Computational protocol: Dual kinase bromodomain inhibitors for rationally designed polypharmacology

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Protocol publication

[…] In all cases crystals were cryo-protected using the well solution supplemented with additional ethylene glycol and were flash frozen in liquid nitrogen. Data were collected at a Rigaku FRE Superbright using an RAXIS-VI detector. Indexing and integration was carried out using XDS, and scaling was performed with SCALA. Initial phases were calculated by molecular replacement with PHASER using an ensemble of known bromodomain models (PDB IDs 2OSS, 2OUO, 2GRC, 2OO1, 3DAI, 3D7C, 3DWY). Initial models were built by ARP/wARP and building was completed manually with COOT. Refinement was carried out in REFMAC5. Thermal motions were analyzed using TLSMD and hydrogen atoms were included in late refinement cycles. Data collection and refinement statistics can be found in . The models and structure factors have been deposited with PDB accession codes: 4OGJ (BRD4(1)/TG-101348) and 4OGI (BRD4(1)/ BI-2536). […]

Pipeline specifications

Software tools XDS, CCP4, ARP/wARP, Coot, REFMAC5
Applications Small-angle scattering, Protein structure analysis
Diseases Neoplasms